Drug-herb and Drug-drug Interactions in Oncology

DDIs

Comorbidities are present in 54.4% of patients with cancer, with hypertension (38.2%) and diabetes mellitus (14.1%) being the most common, according to the prospective study. Both of these conditions typically require management with pharmaceuticals, posing the risk of DDIs.²

Tyrosine kinase inhibitors (TKIs), for example, interact with many antidiabetic agents, including metformin, glitazones, glinides, and glibenclamide, resulting in exposure changes to the TKI or the antidiabetic agent, potentially affecting efficacy or toxicity of both.⁵

Similar interactions have been identified with antihypertensive medications and TKIs, including angiotensin-converting enzyme inhibitors and losartan.

In the 2017 study, 17.4% of patients were identified to have potentially clinically relevant DDIs, primarily pharmacokinetic (86.1%) followed by pharmacodynamic (13.9%) interactions. Nearly 3% of patients experienced a clinical consequence from a DDI.²

In another study, 67 different DDIs were identified among 73 pediatric patients with cancer, and 11 of the DDIs required intervention. Complementary alternative medicine and dietary supplements did not, however, result in DDIs in this study.⁶

Over-the-counter drugs were used by 16.1% of patients in the 2017 study and some, such as acetaminophen and ibuprofen, had the potential to cause DDIs. In this study, interestingly, primarily OTC combinations were assigned an “X” risk rating, indicating that patients should avoid use. Ibuprofen and methotrexate, for example, were assigned an X risk rating because of the decreased renal excretion of methotrexate.

Another combination with an X risk rating was omeprazole and erlotinib, due to the reduced absorption of erlotinib.

Yet a pooled analysis of phase 2 and 3 trials of 2188 patients with metastatic renal cell carcinoma taking axitinib, sorafenib, or sunitinib found that proton pump inhibitor use, such as omeprazole, did not affect objective response, progression-free survival, or overall survival, suggesting that if absorption of these agents was reduced, it was not clinically significant.⁷

Similarly, acetaminophen and imatinib were assigned a risk rating of “C” — meaning to monitor during therapy — due to the increased risk of hepatotoxicity.² Yet In the pediatric study OTC medications did not result in DDIs.⁶

These discrepancies highlight the need for researchers to conduct studies to understand the clinical, rather than just theoretical, risk of DDIs.

References

1. Izzo AA, Hoon-Kim S, Radhakrishnan R, Williamson EM. A critical approach to evaluating clinical efficacy, adverse events and drug interactions of herbal remedies. Phytotherapy Res. 2016;30:691-700. doi: 10.1002/ptr.5591
2. Ramos-Esquivel A. Viquez-Jaikel A, Fernandez C. Potential drug-drug and herb-drug interactions in patients with cancer: a prospective study of medication surveillance. J Oncol Pract. 2017;13(7):e613-22. doi: 10.1200/JOP.2017.020859
3. Gupta D, Lis CG, Birdsall TC, Grutsch JF. The use of dietary supplements in a community hospital comprehensive cancer center: implications for conventional cancer care. Support Care Cancer. 2005;13:912-9.
4. Alsanad SM, Howard RL, Williamson EM. An assessment of the impact of herb-drug combinations used by cancer patients. BMC Compliment Altern Med. 2016;16:393.
5. Haouala A, Widmer N, Duchosal MA, Montemurro M, Buclin T, Decosterd LA. Drug interactions with the tyrosine kinase inhibitors imatinib, dasatinib, and nilotinib. Blood. 2011;117:e75-87. doi: 10.1182/blood-2010-07-294330
6. Balk TE, van der Sijs IH, van Gelder T, et al. Drug-drug interactions in pediatric oncology patients. Pediatr Blood Cancer. 2017;64. doi: 10.1002/pbc.26410
7. Lalani AA, McKay RR, Lin X, Simantov R, Kaymakcalan MD, Choueiri TK. Proton pump inhibitors and survival outcomes in patients with metastatic renal cell carcinoma. Clin Genitourin Cancer. 2017 May 31. doi: 10.1016/j.clgc.2017.05.019 [Epub ahead of print]